This project is concerned with the organization, structure and function of the red cell membrane skeleton in certain inherited hematological disorders, especially hereditary spherocytosis, hereditary elliptocytosis, and four hemolytic anemias in mice due to spectrin deficiency. The study is divided into four parts: (1) Purification of the major membrane skeletal proteins. (2) Development of screening assays for defective skeletal organization and specific assays for the interactions of spectrin with itself, actin, and its membrane receptor. (3) Use of these assays to probe for and characterize the membrane skeleton in hereditary spherocytosis, hereditary elliptocytosis, and selected other membrane disorders including: hereditary stomatocytosis, hereditary xerocytosis, hereditary pyropoikilocytosis, and beta-thalassemia. (4) Investigation of the cause of spectrin deficiency in the mutant mouse hemolytic anemias and the consequences of this deficiency on membrane function.